mmg_233_2013_genetics_genomicswikiaorg-20200214-history
Drosophila melanogaster: Sex-Linked Genes
Genetic linkage , or linkage disequilibrium, is the tendency of genes that are adjacent to one another to be inherited together on the same chromosome during meiosis. Sex linked genes are genes that are inherited with one of the sex chromosomes. This is most often called X-linked inheritance because very few genes are inherited on the Y chromosome. History Gregor Mendel is often consider "lucky" in his initial genetic studies because he chose a genetically simple organism, with distinct traits, that were often unlinked and inherited by the principle of independent assortment. However, researchers began to see that some of their traits were appearing much more often than what Mendel's principle would have predicted. The first to notice this phenomena was William Bateson, Edith Rebecca Saunders and Reginald C. Punnett in 1905 with their work with pea plants, in which they predicted that alleles must somehow be coupled together. However, the answer to this phenomenon did not appear until Thomas Hunt Morgan used Drosophila melanogaster to show that linked genes are physically located close together on a chromosome and therefore inherited together (1). Classical Genetic Linkage Studies: Morgan's Simple Breeding Experiment In the early twentieth century, Morgan and his student's were vigurously working to create a fruit fly, Drosophila melanogaster, with a unique phenotype by exposing the flies to heat, acids, bases, X-rays and other chemicals. However, Morgan noticed a a white-eyed fruit fly that had mysteriously appeared without bombardment of mutagenic treatments. Morgan immediately crossed the white-eyed male fruit fly to it's wild type, red eyed female sisters. He then mated the heterozygous red-eyed F1 progeny to obtain the F2 generation. Morgan obtained the following results: These results deviated from Mendel's predictions in a few ways. Firstly, if the white-eyed trait was truly recessive and assorted independently, then the F2 progeny should have displayed a 3:1 ratio of red-eyed to white-eyed fruit flies. However, Morgan saw that only males had the white-eyed phenotype. Because Morgan only saw that males expressed the white-eyed phenotype, he thought that the trait for white-eyes was a "sex limited trait". He thought that perhaps the gene for eye color was located very closely to the "sex factor" and, therefore, were inherited together. We now know that he was describing that the gene for eye color is located on the X chromosome. However, Morgan worded this a bit differently. He said that males were heterozygous for sex and, therefore, spermatozoa carrying the white-eyed allele did not have the sex factor, whereas red-eyed males had the sex factor. To look further into this hypothesis, Morgan crossed his original white-eyed male fruit fly with the F1 red-eyed female progeny. He found that all four classes of individuals (red-eyed males/females and white-eyed males/females) occured in roughly equal proportions. We now call this "sex linked" or "X-linked" inheritance, although Morgan called it sex limited. A Punnett square can be seen in Figure 1. Here you can find Morgan's original paper entitled "Sex limited inheritance in Drosophila" published in Science (1910). It is accompanied by a review written to clarify some of the language and symbols Morgan uses, as they are different than any used today. Model Organism: Drosophila melanogaster The fruit fly, Drosophila melanogaster, has been one of the most important model organisms in genetics. For one, Drosophila has an extremely short life cycle, reaching maturation after 4.5 days. In addition, Drosophila is a diploid organism and displays sexual dimorphism, meaning there are males and females. Drosophila females are XX and Drosophila males are X0, although the mechanism of sex determination is slightly different in humans. Sex in Drosophila is determined by the number of X chromosomes. Males are determined by the absence of one X chromosome and, therefore, do not have a Y chromosome, the male determining factor in humans. This can be illustrated in Figure 2, showing atypical numbers of chromosomes. Sex-Linked Genes in Drosophila melanogaster Morgan's discovery that genes were located on chromosomes helped transform biology into an experimental science. Now, new methods have evolved to map the genes on chromosomes that are much more complicated than Morgan's breeding experiments. Figure 3 shows a map of the Drosophila X chromosome in which genes were placed in order, distal to proximal, by hybridization to cloned sequences (HYB), hybridization to oligonucleotides (OL) and determination of sequence tagged sites (STS) (3). References #Discovery and Types of Genetic Linkage. http://www.nature.com/scitable/topicpage/discovery-and-types-of-genetic-linkage-500 #The DNA Learning Center. http://www.dnalc.org/view/15005-Thomas-Hunt-Morgan.html #A physical map of the X chromosome of Drosophila melanogaster: Cosmid contigs and sequence tagged sites. http://www.genetics.org/content/139/4/1631.full.pdf #Sex limited inheritance in Drosophila. http://www.esp.org/foundations/genetics/classical/thm-10a.pdf